Pneumonia is a major cause of hospitalization, mortality, and healthcare cost. 1,2 The diagnosis involves clinical features plus radiographic evidence of infection. Hospital-acquired pneumonia (HAP) is defined by the Infectious Disease Society of America (IDSA) as a pneumonia that occurs ≥48 hours after admission and is not associated with mechanical ventilation. 3
IDSA recommendations suggest that patients with suspected HAP be treated based on results of noninvasively obtained sputum cultures rather than being treated empirically. 3 This recommendation is graded as weak with low-quality evidence based on a lack of both evidence showing that respiratory cultures improve clinical outcomes and studies examining the yield of noninvasive collection methods. 4,5 However, resistant pathogens lead to a risk of inadequate empiric therapy, which is associated with increased mortality. 6 Culture data may provide an opportunity for escalation or de-escalation of antibiotic coverage. IDSA recommendations for microbiologic sampling are thus aimed at increasing appropriate coverage and minimizing unnecessary antibiotic exposure.
While the yield and clinical utility of sputum culture in community-acquired pneumonia has been studied extensively, data examining the yield of sputum culture in HAP (non–ventilator-associated pneumonia [non-VAP]) are sparse. In 1 small single-center study, researchers demonstrated positive sputum cultures in 17/35 (48.6%) patients with radiographically confirmed cases of HAP, 7 while in another study, researchers demonstrated positive sputum cultures in 57/63 (90.5%). 8 We aimed to identify the frequency with which sputum cultures positively identify an organism, identify predictors of positive sputum cultures, and characterize the microbiology of sputum cultures in a large cohort of HAP cases.
We conducted a retrospective cohort study of patients admitted to a large academic medical center in Boston, Massachusetts, from January 2007 to July 2013. All patients ≥18 years of age were eligible for inclusion. We excluded outside hospital transfers, those with a length of hospitalization <48 hours, and psychiatric admissions.
The study was approved by the institutional review board at the Beth Israel Deaconess Medical Center and granted a waiver of informed consent. Data were collected from electronic databases and supplemented by chart review.
We defined HAP as pneumonia occurring at least 48 hours after admission, consistent with American Thoracic Society and IDSA criteria.3 To identify cases, we reviewed the charts of all admissions identified as having a discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for bacterial pneumonia (481, 482, 483, 485, 486, 507), indicated as not “present-on-admission.” We validated that the treating clinician had clinically diagnosed pneumonia and initiated antibiotics for this purpose by performing chart review. We reviewed the radiologist interpretation of radiographs surrounding the date of the clinical diagnosis of pneumonia to confirm the presence of a new opacity. Uncertain cases (with respect to either the presence of pneumonia or the timing of the diagnosis) were reviewed by a second member of the study team and, in the case of disagreement, adjudicated by a third member of the study team. Only the first clinically validated HAP per hospitalization was included in the analysis. To focus on HAP rather than VAP, we excluded hospitalizations in which the date of a procedure code for mechanical ventilation preceded the date of pneumonia diagnosis.
In our analysis, we used sputum samples obtained from expectorated or induced samples to evaluate the yield of noninvasive sputum sampling, as recommended by the IDSA. We included sputum samples collected ≥48 hours after admission and within 7 days of the clinical diagnosis of HAP. Sputum samples with >10 epithelial cells per high-power field (hpf) were considered to be contaminated. Among noncontaminated samples, positive sputum cultures were defined as those with a microbiologic diagnosis other than “oral flora,” while those with no growth or growth of oral flora or only yeast were considered to be negative. The hospital’s microbiology laboratory does not routinely provide species identification for Gram-negative rods (GNRs) growing on culture in the presence of growth of ≥3 other colony types. We considered such GNRs (not further speciated) to represent a positive culture result in our analysis given that colonization versus pathogenicity is a clinical distinction and, as such, these results may impact antibiotic choice.
Data were analyzed by using SAS software, version 9.3. We used a 2-sided P value of <0.05 to indicate statistical significance for all comparisons. We used the χ2 test and the nonparametric median test for unadjusted comparisons.
To identify predictors of a positive (versus negative or contaminated) sputum culture among patients with HAP, we used a generalized estimating equation model with a Poisson distribution error term, log link, and first-order autoregressive correlation structure to account for multiple sputum specimens per patient. We combined culture negative and contaminated samples to highlight the clinical utility of sputum culture in a real-world setting. Potential predictors chosen based on clinical grounds included all variables listed in Table 1. We defined comorbidities specified in Table 1 via ICD-9-CM secondary diagnosis codes and diagnosis related groups (DRGs) using Healthcare Cost and Utilization Project Comorbidity Software, version 3.7, based on the work of Elixhauser et al.9,10; dialysis use was defined by an ICD-9-CM procedure code of 39.95; inpatient steroid use was defined by a hospital pharmacy charge for a systemic steroid in the 7 days preceding the sputum sample.
There were 230,635 hospitalizations of patients ≥18 years of age from January 2007 to July 2013. After excluding outside hospital transfers (n = 14,422), hospitalizations <48 hours in duration (n = 59,774), and psychiatric hospitalizations (n = 9887), there were 146,552 hospitalizations in the cohort.
The top 3 bacterial organisms cultured from sputum samples were GNRs not further speciated (25.9%), Staphylococcus aureus (21.0%), and Pseudomonas aeruginosa (14.8%). The frequencies of isolated microorganisms are presented in Table 2.
In an adjusted analysis (Table 1), the significant predictors of a positive sputum culture were chronic lung disease (relative risk [RR] = 2.0; 95% confidence interval [CI], 1.2-3.4) and steroid use (RR = 1.8; 95% CI, 1.1-3.2).
To our knowledge, our study is the first to assess the predictors of positive sputum culture among patients with HAP (non-VAP) who had sputum samples obtained noninvasively, and this study is larger than prior studies in which researchers reported on sputum culture yield in HAP. Sputum samples were obtained in 29.4% cases of clinically diagnosed HAP. Although 87% of specimens obtained were culture-negative or contaminated, 13% yielded a bacterial organism. Although we do not report the antibiotic sensitivity patterns of the isolated organisms, the organisms identified frequently demonstrate antibiotic resistance, highlighting the potential for both antibiotic escalation and de-escalation based on sputum culture. In a multivariable model, presence of chronic lung disease and steroid use in the preceding week were both significantly associated with culture positivity.
The retrospective nature of the study raises the possibility of selection bias from systematic differences between the 29.4% of patients with HAP who had sputum collected and those who did not. Patients with sputum cultures were similar to patients without cultures in most measured characteristics, but we are unable to know what the yield of noninvasive sputum culture would have been had all patients with HAP been sampled. As such, our findings reflect the yield of sputum culture among patients with HAP for whom cultures were successfully obtained. It is not clear why only 29.4% of HAP patients received IDSA guideline-concordant care, but similar rates of culture use are reported elsewhere.7 While physician decision-making could have contributed to this finding, it is also possible that many sick, hospitalized patients are simply unable to produce sputum for analysis. In future studies, researchers should examine barriers to guideline-concordant care.
We considered a culture result of GNRs (not further speciated) as positive in our analysis because this result indicates growth of mixed bacterial types, the pathogenicity of which is a clinical determination. Physicians may request speciation and antibiotic sensitivities and, as such, these results have the potential to impact antibiotic choice. Had we considered such cultures to be negative or contaminated, the rate of culture positivity would have been only slightly reduced from 63/478 (13.2%) to 50/478 (10.5%).
The strengths of our study include the chart-based validation of administratively identified cases of pneumonia and a large cohort. There are also limitations. The single-center nature of the study has implications for pretest probability and generalizability. Additionally, in our study, we did not examine outcomes among patients treated empirically versus those treated based on sputum culture results. Finally, our reliance on administrative codes to identify cases of HAP for subsequent validation could have resulted in incomplete capture of HAP cases.
In conclusion, in our study, we provide an estimate of the diagnostic yield of sputum culture in a large cohort with chart-validated HAP, a description of HAP microbiology, and predictors of positive sputum culture. Thirteen percent of patients who had sputum culture testing received a microbiologic diagnosis. Because of the relative ease of obtaining a sputum sample and the microbiologic distribution in our study (representing a mix of commonly drug-resistant pathogens and more typical community-acquired pathogens), we suggest that sputum culture in HAP is a useful diagnostic tool with the potential to inform antibiotic escalation or de-escalation.
Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Marcantonio was funded by grant number K24AG035075 from the National Institute on Aging. The funding organizations had no involvement in any aspect of the study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
No conflicts of interest apply for any of the authors.